PPARs单核苷酸多态性基因-基因交互作用对脂蛋白（a）的影响  

Association of peroxisome proliferator-activated receptor single-nucleotide polymorphisms and gene-gene interactions with the lipoprotein （a）

作　　者：解惠坚[1] 海波[1] 郭志荣[1] 周正元[2] 武鸣[3] 陈秋[4] 俞浩[3] 刘萌萌[1] 

机构地区：[1]苏州大学医学部公共卫生学院流行病与卫生统计教研室,215123 [2]江苏省常熟市疾病预防控制中心 [3]江苏省疾病预防控制中心慢病科 [4]苏州大学医学部放射生物学教研室

出　　处：《中华内分泌代谢杂志》2014年第5期402-407,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：卫生部科学研究基金项目（WKJ2004-2-014）

摘　　要：目的探讨过氧化物酶体增殖物激活受体（PPAR）10个单核苷酸多态性（SNP）与血浆脂蛋白（a）的关联，以及多个SNP间交互作用对脂蛋白（a）水平的影响。方法研究对象均来自于“江苏省多代谢异常和代谢综合征综合防治研究”队列人群，抽取644名研究对象，对其基线血标本进行PPARs的10个SNP（rs135539、rs4253778、rs1800206，rs2016520、rs9794、rs10865710、rs1805192、rs709158、rs3856806、rs4684847）检测，以随访时所测血浆脂蛋白（a）水平作为结局。运用SNPstats软件分析SNPs与脂蛋白（a）的关联，采用广义多因子降维法（GMDR）模型，调整环境协变量后，检测10个SNPs基因．基因交互作用。结果与野生型（LL）相比，PPARα rs1800206位点的突变型（LV＋VV）携带者脂蛋白（a）水平显著增高（平均差值44．26mg／L，95％CI 18．23-70．30mg／L，P〈0．01），未发现其他SNP与脂蛋白（a）存在显著关联。GMDR模型结果显示二阶、三阶和五阶交互作用模型均有统计学意义（均P〈0．01），其中包括rs135539、rs10865710、rs1800206、rs1805192和rs4684847的五阶模型交叉验证一致性为10／10，平均检验准确度为0．6848，为最优模型。结论rs1800206多态性与脂蛋白（a）水平有关联，PPARα的rs1800206、rs135539和PPARγ的rs10865710、rs1805192、rs4684847这5个SNP间的基因一基因交互作用显著影响脂蛋白（a）水平。Objective To examine the associations of 10 single-nucleotide polymorphisms （SNPs） in peroxisome proliferator-activated receptor （PPARs） gene with lipoprotein （a） level, and to investigate if there is gene- gene interaction among the SNPs on lipoprotein （a） level. Methods Totally 644 subjects （ 234 men and 410 women ） were enrolled from Prevention of Multiple Metabolic Disorders and Metabolic Syndrome Study Cohort, which was an urban community survey study conducted in Jiangsu province. Ten SNPs in PPARα （rs135539, rs4253778, rs1800206）, PPARδ （rs2016520, rs9794）, and PPARγ （rs10865710, rs1805192, rs709158, rs3856806, rs4684847 ）were genotyped and analyzed. SNPstats program was used to examine the association between the SNPs and lipoprotein （ a ）. Gene-gene interactions were analyzed with generalized multifactor dimensionality reduction （GMDR） method. Results The frequencies of genotypes of the 10 SNPs all obeyed the law of Hardy-Weinberg equilibrium. After adjusted for gender, age, smoking, alcohol, waist circumference, fasting plasma glucose, total cholesterol, triglycerides, and physical activity, lipoprotein （a） level was significantly higher in the subjects with mutant（LV＋VV） comparing to those with widetype （LL） （ mean difference 44.26 mg/L, 95% CI 18.23-70.30 mg/L, P〈 0. 01 ）. There were no significant associations of other 9 SNPs in PPARs gene with lipoprotein （a） level. After multiple variables were adjusted, gene-gene interactions among rs1800206, rs135539 in PPARα and rs10865710, rs1805192, rs4684847 in PPARγ on lipoprotein （a） level were significant （all P 〈 0. 01 ）, with prediction accuracy 0. 684 8 and cross-validation consistency 10/10. Conclusion It was suggested that mutation of rs1800206 was associated with a higher level of lipoprotein （a）. In addition, a gene-gene interaction on lipoprotein （a） level was identified among rs1800206, rs135539, rs10865710, rs1805192, and rs4684847.

关 键 词：脂蛋白(a) 过氧化物酶体增殖物激活受体 多态性 单核苷酸 交互作用 

分 类 号：R589[医药卫生—内分泌] R181.3[医药卫生—内科学]